A continuing long-range interest of the program is to examine the pathophysiology of renal disease and uremia by the use of physiological and biochemical techniques. Studies will be continued in an effort to clarify the functional characteristics of the chronically diseased kidney, and in particular to define the changes in Na, K and H ion reabsorption by deep nephrons and papillary collecting ducts, and renal mass is decreased. To define the role of endogenous prostaglandins as modulators of total and regional blood flow and GFR in normal and obstructed kidneys and to correlate biochemical alterations in prostaglandin synthesis with functional parameters. To study the pathogenesis and modalities of treatment of glomerulonephritis and minimal change nephrotic syndrome in humans and experimental animals. To characterize the effects of chronic renal insufficiency particularly as they relate to metabolic alterations. Studies will be continued on the pathogenesis and prevention of secondary hyperparathyroidism in chronic renal disease. These studies include the investigation of the peripheral metabolism of parathyroid hormone and its fragments by isolated perfused bone and kidney from normal and uremic dogs subjected to dietary changes in Ca, Mg, PO4, H ion and vitamin D. To study the role of the liver in the in vivo metabolism of intact PTH and the effects of the hormone on hepatic carbohydrate metabolism. To study the effect of PTH on uptake and release of myoinositol at the cellular level. To determine the effect of uremia on glucose and amino acid metabolism by isolated skeletal muscle and to define the effects of dialysis and different dietary regimes on protein metabolism in children with end-stage renal disease. A second area of interest relate to the biochemical events regulating basal and hormonal stimulated ion transport across isolated membranes (toad bladder, isolated perfused renal tubules).